Romero-Estrada, J.H.; Montaño, L.F.; Rendón-Huerta, E.P. Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression in H. pylori LPS-Stimulated AGS Cells. Int. J. Mol. Sci.2023, 24, 13974.
Romero-Estrada, J.H.; Montaño, L.F.; Rendón-Huerta, E.P. Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression in H. pylori LPS-Stimulated AGS Cells. Int. J. Mol. Sci. 2023, 24, 13974.
Romero-Estrada, J.H.; Montaño, L.F.; Rendón-Huerta, E.P. Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression in H. pylori LPS-Stimulated AGS Cells. Int. J. Mol. Sci.2023, 24, 13974.
Romero-Estrada, J.H.; Montaño, L.F.; Rendón-Huerta, E.P. Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression in H. pylori LPS-Stimulated AGS Cells. Int. J. Mol. Sci. 2023, 24, 13974.
Abstract
Aberrant expression of the tight junction protein claudin 6 (CLDN6) is a hallmark of gastric can-cer progression. Its expression is regulated by the transcription factor CREB. But in H. pylo-ri-induced gastric cancer there is no information regarding what transcription factors in-duce/upregulate the expression of CLDN6. We aimed to identify if CREB and YY1 regulate the expression of CLDN6 and the site where they bind to the promoter sequence. Bioinformatics analysis, H. pylori LPS, YY1 and CREB silencing, western blot, luciferase assays, and chromatin immunoprecipitation experiments were performed using the gastric adenocarcinoma cell line AGS. A gen reporter assay suggested that the initial 2000 bp contains the regulatory sequence as-sociated with CLDN6 transcription; the luciferase assay demonstrated three different regions with transcriptional activity, but the -901 to -1421 bp region displayed the maximal transcrip-tional activity in response to LPS. Fragment 1279-1421 showed CREB and surprisingly YY1 oc-cupancy. Sequential ChIP experiments confirmed that YY1 and CREB interact in the 1279-1421 region. Our results suggest that CLDN6 expression is regulated by the binding of YY1 and CREB in the 901-1421 enhancer in which a non-described interaction of YY1 with CREB was established in the 1279-1421 region.
Biology and Life Sciences, Biochemistry and Molecular Biology
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